Post-translational modifications of EMT transcriptional factors in cancer metastasis

Abstract

Metastasis is an important reason for death of cancer patients which characterized as the formation of secondary cancers at distant sites. Epithelial– mesenchymal transition (EMT) is a dynamic process that appear to facilitate tumor metastasis in various cancers by switching epithelial cells into mesenchymal properties. Although previous investigation suggested a key role of EMT transcriptional factors in suppression of E-cadherin, the association of these factors with other cellular regulators in cancer metastasis need to be fully elucidated. Post-translational modifications (PTMs), such as acetylation and phosphorylation, have emerged as an important mechanism to modulate biological behavior of substrate proteins. In this review, we summarized protein modification and subsequent function changes of Snail, Twist and ZEB, as well as their influence on tumor progression. Acetylation of EMT transcriptional factors usually cause nuclear localization and/or protein stabilization thus contribute to E-cadherin repression. Besides, Twist and ZEB were phosphorylated by diverse kinases to promote metastasis in many cancers, while Snail was negatively regulated by phosphorylation to degradation. Then, the potential of therapy for metastasis by targeting PTMs-involved regulation of EMT transcriptional factors were discussed.

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial–Mesenchymal Transition in Cancer

“…These are the major players of the cell cycle, thus deregulation of their phosphorylation–dephosphorylation state can contribute to cancer progression [160]. Furthermore, phosphorylation of effector proteins, like the TFs Snail, Twist, and ZEB, also contributes to EMT and cancer progression [161].…”

The Post-Translational Regulation of Epithelial–Mesenchymal Transition-Inducing Transcription Factors in Cancer Metastasis

“…The other well-known PTM of Twist1 is acetylation [ 151 ]. Studies have revealed that Twist1 interacts with p300 or p300/CBP-associated factor (PCAF), a well-known HAT and promotes EMT by suppressing the expression of E-cadherin [ 152 ] and p53 [ 153 ].…”

Is There an Interconnection between Epithelial–Mesenchymal Transition (EMT) and Telomere Shortening in Aging?

“…This process culminates in the expression of genes with the function of encoding EMT transcription factors (EMT-TFs) [ 4 , 21 , 22 ]. In EMT, three major groups of EMT-TFs play vital roles, including SNAI (Snail and Slug), ZEB (ZEB1 and ZEB2) and TWIST (TWIST1 and TWIST2) [ 23 , 24 , 25 , 26 ], which repress the expression of E-cadherin, thus causing the disassembly of cell–cell junctions and inducing EMT [ 27 , 28 ]. As the main component, TGF-β is also involved in many signaling pathways contributing to the development of EMT, such as the TGF-β signaling pathway [ 29 ], the WNT signaling pathway [ 4 , 30 ], and the Smad Signaling pathway [ 31 , 32 ], which regulates the EMT process.…”